1. Field of the Invention
The present invention concerns the decarboxylation of 3,5-bis(haloalkyl)-pyrazole-4-carboxylic acid derivatives for the synthesis of 3,5-bis(haloalkyl)-pyrazole derivatives.
2. Description of Related Art
3,5-bis(haloalkyl)-pyrazole derivatives are important building blocks for the preparation of crop protection chemicals, as those described in WO 2007/014290, WO 2008/013925, WO 2008/013622, WO 2008/091594, WO 2008/091580, WO 2009/055514, WO 2009/094407, WO 2009/094445, WO 2009/132785, WO 2010/037479, WO 2010/065579, WO 2010/066353, WO 2010/123791, WO 2010/149275, WO 2011/051243, WO 2011/085170, WO 2011/076699.
Decarboxylation reactions of 4-carboxylic acid pyrazoles bearing one haloalkyl substituent are poorly developed: only two references can be found in the literature. Indeed, the resulting products are generally very volatile, thus very difficult to isolate.
5-Methyl-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid is transformed into 5-methyl-1-phenyl-3-trifluoromethyl pyrazole by reaction with copper powder in quinoline (K. Tanaka et al., Bull. Chem. Soc. Jpn., 1986, 2631-2632), but the yield merely reaches 32%.
Maggio et al. describe the decarboxylation of 5-amino-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (Eur. J. Med. Chem., 2008, 2386-2394) by heating it neat at its melting point for one hour with a low yield of 30%.
No method is described for the decarboxylation of a 4-carboxylic acid pyrazole bearing more than one haloalkyl substituent.
Guillou et al. describe a copper-catalyzed protodecarboxylation on pyrazoles (Tetrahedron 2010, 66, 2654-2663) using Cu2O in the presence of 1,10-phenanthroline and cesium carbonate. The reaction is carried out in DMF and under harsh conditions (microwave irradiation for 2 h at 200° C.). Metal-catalyzed protodecarboxylation reactions are described by Goossen et al. (Synthesis, 2012, 184-193) using copper and silver catalysts. These reactions are performed on aromatic and heteroaromatic carboxylic acids, however this reaction is not shown for the substrates having bis(haloalkyl)-substituents. Bis(haloalkyl)-substituents on heteroaromatic carboxylic acids are known to effect decarboxylation reactions in a negative way (e.g. very low yield or no yield).